Microwave catheter apparatuses, systems, and methods for renal neuromodulation

ABSTRACT

Microwave catheter apparatuses, systems, and methods for achieving renal neuromodulation by intravascular access are disclosed herein. One aspect of the present application, for example, is directed to apparatuses, systems, and methods that incorporate a catheter treatment device comprising an elongated shaft. The elongated shaft is sized and configured to deliver a microwave transmission element to a renal artery via an intravascular path. Renal neuromodulation may be achieved via dielectric heating in the presence of microwave irradiation that modulates neural fibers that contribute to renal function or alters vascular structures that feed or perfuse the neural fibers.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. patent application Ser. No.13/281,244, filed Oct. 25, 2011, which claims the benefit of U.S.Provisional Application No. 61/406,534, filed Oct. 25, 2010, andincorporated herein by reference in its entirety.

TECHNICAL FIELD

The technologies disclosed in the present application generally relateto catheter apparatuses, systems, and methods for intravascularneuromodulation. More particularly, the technologies disclosed hereinrelate to microwave catheter apparatuses, systems, and methods forachieving intravascular renal neuromodulation via dielectric heating.

BACKGROUND

The sympathetic nervous system (SNS) is a primarily involuntary bodilycontrol system typically associated with stress responses. Fibers of theSNS innervate tissue in almost every organ system of the human body andcan affect characteristics such as pupil diameter, gut motility, andurinary output. Such regulation can have adaptive utility in maintaininghomeostasis or in preparing the body for rapid response to environmentalfactors. Chronic activation of the SNS, however, is a common maladaptiveresponse that can drive the progression of many disease states.Excessive activation of the renal SNS in particular has been identifiedexperimentally and in humans as a likely contributor to the complexpathophysiology of hypertension, states of volume overload (such asheart failure), and progressive renal disease. For example, radiotracerdilution has demonstrated increased renal norepinephrine (NE) spilloverrates in patients with essential hypertension.

Cardio-renal sympathetic nerve hyperactivity can be particularlypronounced in patients with heart failure. For example, an exaggeratedNE overflow from the heart and kidneys to plasma is often found in thesepatients. Heightened SNS activation commonly characterizes both chronicand end stage renal disease. In patients with end stage renal disease,NE plasma levels above the median have been demonstrated to bepredictive for cardiovascular diseases and several causes of death. Thisis also true for patients suffering from diabetic or contrastnephropathy. Evidence suggests that sensory afferent signals originatingfrom diseased kidneys are major contributors to initiating andsustaining elevated central sympathetic outflow.

Sympathetic nerves innervating the kidneys terminate in the bloodvessels, the juxtaglomerular apparatus, and the renal tubules.Stimulation of the renal sympathetic nerves can cause increased reninrelease, increased sodium (Na⁺) reabsorption, and a reduction of renalblood flow. These neural regulation components of renal function areconsiderably stimulated in disease states characterized by heightenedsympathetic tone and likely contribute to increased blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome (i.e., renal dysfunction as a progressive complication ofchronic heart failure). Pharmacologic strategies to thwart theconsequences of renal efferent sympathetic stimulation include centrallyacting sympatholytic drugs, beta blockers (intended to reduce reninrelease), angiotensin converting enzyme inhibitors and receptor blockers(intended to block the action of angiotensin II and aldosteroneactivation consequent to renin release), and diuretics (intended tocounter the renal sympathetic mediated sodium and water retention).These pharmacologic strategies, however, have significant limitationsincluding limited efficacy, compliance issues, side effects, and others.Accordingly, there is a strong public-health need for alternativetreatment strategies.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a conceptual illustration of the sympathetic nervous system(SNS) and how the brain communicates with the body via the SNS.

FIG. 2 is an enlarged anatomic view of nerves innervating a left kidneyto form the renal plexus surrounding the left renal artery.

FIGS. 3A and 3B provide, respectively, anatomic and conceptual views ofa human body, depicting neural efferent and afferent communicationbetween the brain and kidneys.

FIGS. 4A and 4B are, respectively, anatomic views of the arterial andvenous vasculatures of a human.

FIG. 5 is a perspective view of a microwave system for achievingintravascular renal neuromodulation, comprising a treatment device and amicrowave generator.

FIGS. 6A and 6B are, respectively, a schematic view illustratingplacement of a distal region of the treatment device of FIG. 5 within arenal artery via an intravascular path, and a detailed schematic view ofan embodiment of the distal region within the renal artery for deliveryof microwave energy.

FIG. 7 is a schematic side-sectional view of the distal region of anembodiment of the microwave treatment device of FIG. 5 comprising acoaxial cable feed line and a coaxial antenna microwave transmissionelement.

FIGS. 8A and 8B are schematic side-sectional views of the distal regionof an embodiment of the microwave treatment device of FIG. 5 in alow-profile delivery configuration and in an expanded deployedconfiguration, including a multi-filament centering element.

FIG. 9 is a schematic side-sectional view of the distal region of analternative embodiment of the microwave treatment device of FIGS. 8A and8B comprising an alternative multi-filament centering element.

FIGS. 10A and 10B are, respectively, a schematic side-sectional view anda schematic cross-sectional view along section line 10B-10B of FIG. 10Aof the distal region of an embodiment of the microwave treatment deviceof FIGS. 8A and 8B comprising an expandable balloon centering element.

FIGS. 11A and 11B are schematic cross-sectional views of the distalregion of alternative embodiments of the microwave treatment device ofFIGS. 10A and 10B comprising an alternative expandable balloon centeringelement.

FIG. 12 is a schematic side-sectional view of the distal region ofanother alternative embodiment of the microwave treatment device ofFIGS. 10A and 10B comprising another alternative expandable ballooncentering element having proximal and distal balloons.

FIG. 13 is a schematic side-sectional view of the distal region ofanother alternative embodiment of the microwave treatment device ofFIGS. 10A and 10B comprising another alternative expandable ballooncentering element having conductive electrode traces applied on thesurface of the balloon.

FIGS. 14 and 15 are schematic side-sectional views of the distal regionsof other alternative embodiments of the microwave treatment device ofFIGS. 10A and 10B comprising other alternative expandable ballooncentering elements having one or more shields applied on the surface ofthe balloon.

FIG. 16 is a schematic side-sectional view of the distal region ofanother alternative embodiment of the microwave treatment device ofFIGS. 10A and 10B comprising another alternative expandable balloon thatplaces the microwave antenna off-center within a vessel.

FIG. 17 is a schematic view of the distal region of an embodiment of themicrowave treatment device of FIG. 5 comprising a flow directingelement.

FIG. 18A is a schematic side-sectional view of the distal region of anembodiment of the microwave treatment device of FIG. 5 configured fordelivery over a guide wire.

FIG. 18B is a schematic side-sectional view of the distal region of anembodiment of the microwave treatment device of FIG. 5 configured forrapid exchange delivery.

FIGS. 19A and 19B are schematic side-sectional views of the distalregion of an embodiment of the microwave treatment device of FIG. 5illustrating dynamic variation of the coaxial antenna's radiatingelement.

FIG. 20 is schematic side-sectional view of the distal region of analternative embodiment of the microwave treatment device of FIGS. 19Aand 19B configured for dynamic variation of the coaxial antenna'sradiating element.

FIGS. 21A and 21B are schematic side-sectional views of the distalregion of another alternative embodiment of the microwave treatmentdevice of FIGS. 19A and 19B configured for dynamic variation of thecoaxial antenna's radiating element and for over-the-wire delivery.

FIGS. 22A and 22B are schematic side-sectional views of the distalregions of embodiments of the microwave treatment device of FIG. 5configured for active cooling.

FIG. 23A is a schematic side-sectional view of the distal region of anembodiment of a microwave treatment device having a shielding component.

FIGS. 23B and 23C are cross-sectional views of the microwave treatmentdevice of FIG. 23A.

FIGS. 23D and 23E are schematic side views of the distal region of anembodiment of a microwave treatment device having a shielding componentand deflection capabilities.

DETAILED DESCRIPTION

The present technology is directed to apparatuses, systems, and methodsfor achieving electrically- and/or thermally-induced renalneuromodulation (i.e., rendering neural fibers that innervate the kidneyinert or inactive or otherwise completely or partially reduced infunction) by percutaneous transluminal intravascular access. Inparticular, embodiments of the present technology relate to microwaveapparatuses, systems, and methods that incorporate a catheter treatmentdevice. The catheter treatment device may comprise an elongated shaftsized and configured to deliver at least one microwave transmissionelement within a renal artery via an intravascular path (e.g., a femoralartery, an iliac artery and the aorta, a transradial approach, oranother suitable intravascular path). In one embodiment, for example,the microwave transmission element comprises an antenna that radiatesmicrowaves within the renal artery in order to induce dielectric heatingof target renal nerves or of vascular structures that perfuse targetrenal nerves. Microwaves are generated by a microwave generator,transferred along a feed or transmission line, and then radiated by theantenna. The microwave generator may be positioned along or near aproximal region of the elongated shaft external to the patient, whilethe feed line extends along or within the elongated shaft, and theantenna is positioned along a distal region of the shaft configured forplacement in the renal artery via the intravascular path.

Specific details of several embodiments of the technology are describedbelow with reference to FIGS. 1-23E. Although many of the embodimentsare described below with respect to devices, systems, and methods forintravascular modulation of renal nerves using microwave apparatuses,other applications and other embodiments in addition to those describedherein are within the scope of the technology. Additionally, severalother embodiments of the technology can have different configurations,components, or procedures from those described herein. A person ofordinary skill in the art, therefore, will accordingly understand thatthe technology can have other embodiments with additional elements, orthe technology can have other embodiments without several of thefeatures shown and described below with reference to FIGS. 1-23E.

As used herein, the terms “distal” and “proximal” define a position ordirection with respect to the treating clinician or the clinician'scontrol device (e.g., a handle assembly). “Distal” or “distally” are aposition distant from or in a direction away from the clinician orclinician's control device. “Proximal” and “proximally” are a positionnear or in a direction toward the clinician or the clinician's controldevice.

I. Pertinent Anatomy and Physiology

The following discussion provides various details regarding pertinentpatient anatomy and physiology. This section is intended to provideadditional context regarding the disclosed technology and thetherapeutic benefits associated with renal denervation, and tosupplement and expand upon the disclosure herein regarding the relevantanatomy and physiology. For example, as mentioned below, severalproperties of the renal vasculature may inform the design of treatmentdevices and associated methods for achieving renal neuromodulation viaintravascular access, and impose specific design requirements for suchdevices. Specific design requirements may include accessing the renalartery, facilitating stable contact between the energy delivery elementsof such devices and a luminal surface or wall of the renal artery,and/or effectively modulating the renal nerves with the neuromodulatoryapparatus.

A. The Sympathetic Nervous System

The Sympathetic Nervous System (SNS) is a branch of the autonomicnervous system along with the enteric nervous system and parasympatheticnervous system. It is always active at a basal level (called sympathetictone) and becomes more active during times of stress. Like other partsof the nervous system, the sympathetic nervous system operates through aseries of interconnected neurons. Sympathetic neurons are frequentlyconsidered part of the peripheral nervous system (PNS), although manylie within the central nervous system (CNS). Sympathetic neurons of thespinal cord (which is part of the CNS) communicate with peripheralsympathetic neurons via a series of sympathetic ganglia. Within theganglia, spinal cord sympathetic neurons join peripheral sympatheticneurons through synapses. Spinal cord sympathetic neurons are thereforecalled presynaptic (or preganglionic) neurons, while peripheralsympathetic neurons are called postsynaptic (or postganglionic) neurons.

At synapses within the sympathetic ganglia, preganglionic sympatheticneurons release acetylcholine, a chemical messenger that binds andactivates nicotinic acetylcholine receptors on postganglionic neurons.In response to this stimulus, postganglionic neurons principally releasenoradrenaline (norepinephrine). Prolonged activation may elicit therelease of adrenaline from the adrenal medulla.

Once released, norepinephrine and epinephrine bind adrenergic receptorson peripheral tissues. Binding to adrenergic receptors causes a neuronaland hormonal response. The physiologic manifestations include pupildilation, increased heart rate, occasional vomiting, and increased bloodpressure. Increased sweating is also seen due to binding of cholinergicreceptors of the sweat glands.

The sympathetic nervous system is responsible for up- anddown-regulating many homeostatic mechanisms in living organisms. Fibersfrom the SNS innervate tissues in almost every organ system, providingat least some regulatory function to things as diverse as pupildiameter, gut motility, and urinary output. This response is also knownas sympatho-adrenal response of the body, as the preganglionicsympathetic fibers that end in the adrenal medulla (but also all othersympathetic fibers) secrete acetylcholine, which activates the secretionof adrenaline (epinephrine) and to a lesser extent noradrenaline(norepinephrine). Therefore, this response that acts primarily on thecardiovascular system is mediated directly via impulses transmittedthrough the sympathetic nervous system and indirectly via catecholaminessecreted from the adrenal medulla.

Science typically looks at the SNS as an automatic regulation system,that is, one that operates without the intervention of consciousthought. Some evolutionary theorists suggest that the sympatheticnervous system operated in early organisms to maintain survival as thesympathetic nervous system is responsible for priming the body foraction. One example of this priming is in the moments before waking, inwhich sympathetic outflow spontaneously increases in preparation foraction.

1. The Sympathetic Chain

As shown in FIG. 1, the SNS provides a network of nerves that allows thebrain to communicate with the body. Sympathetic nerves originate insidethe vertebral column, toward the middle of the spinal cord in theintermediolateral cell column (or lateral horn), beginning at the firstthoracic segment of the spinal cord and are thought to extend to thesecond or third lumbar segments. Because its cells begin in the thoracicand lumbar regions of the spinal cord, the SNS is said to have athoracolumbar outflow. Axons of these nerves leave the spinal cordthrough the anterior rootlet/root. They pass near the spinal (sensory)ganglion, where they enter the anterior rami of the spinal nerves.However, unlike somatic innervation, they quickly separate out throughwhite rami connectors which connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near theaortic bifurcation) ganglia extending alongside the spinal column.

In order to reach the target organs and glands, the axons should travellong distances in the body, and, to accomplish this, many axons relaytheir message to a second cell through synaptic transmission. The endsof the axons link across a space, the synapse, to the dendrites of thesecond cell. The first cell (the presynaptic cell) sends aneurotransmitter across the synaptic cleft where it activates the secondcell (the postsynaptic cell). The message is then carried to the finaldestination.

In the SNS and other components of the peripheral nervous system, thesesynapses are made at sites called ganglia. The cell that sends its fiberis called a preganglionic cell, while the cell whose fiber leaves theganglion is called a postganglionic cell. As mentioned previously, thepreganglionic cells of the SNS are located between the first thoracic(T1) segment and third lumbar (L3) segments of the spinal cord.Postganglionic cells have their cell bodies in the ganglia and sendtheir axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also thecervical ganglia (superior, middle and inferior), which sendssympathetic nerve fibers to the head and thorax organs, and the celiacand mesenteric ganglia (which send sympathetic fibers to the gut).

2. Innervation of the Kidneys

As FIG. 2 shows, the kidney is innervated by the renal plexus RP, whichis intimately associated with the renal artery. The renal plexus RP isan autonomic plexus that surrounds the renal artery and is embeddedwithin the adventitia of the renal artery. The renal plexus RP extendsalong the renal artery until it arrives at the substance of the kidney.Fibers contributing to the renal plexus RP arise from the celiacganglion, the superior mesenteric ganglion, the aorticorenal ganglionand the aortic plexus. The renal plexus RP, also referred to as therenal nerve, is predominantly comprised of sympathetic components. Thereis no (or at least very minimal) parasympathetic innervation of thekidney.

Preganglionic neuronal cell bodies are located in the intermediolateralcell column of the spinal cord. Preganglionic axons pass through theparavertebral ganglia (they do not synapse) to become the lessersplanchnic nerve, the least splanchnic nerve, first lumbar splanchnicnerve, second lumbar splanchnic nerve, and travel to the celiacganglion, the superior mesenteric ganglion, and the aorticorenalganglion. Postganglionic neuronal cell bodies exit the celiac ganglion,the superior mesenteric ganglion, and the aorticorenal ganglion to therenal plexus RP and are distributed to the renal vasculature.

3. Renal Sympathetic Neural Activity

Messages travel through the SNS in a bidirectional flow. Efferentmessages may trigger changes in different parts of the bodysimultaneously. For example, the sympathetic nervous system mayaccelerate heart rate; widen bronchial passages; decrease motility(movement) of the large intestine; constrict blood vessels; increaseperistalsis in the esophagus; cause pupil dilation, piloerection (goosebumps) and perspiration (sweating); and raise blood pressure. Afferentmessages carry signals from various organs and sensory receptors in thebody to other organs and, particularly, the brain.

Hypertension, heart failure and chronic kidney disease are a few of manydisease states that result from chronic activation of the SNS,especially the renal sympathetic nervous system. Chronic activation ofthe SNS is a maladaptive response that drives the progression of thesedisease states. Pharmaceutical management of therenin-angiotensin-aldosterone system (RAAS) has been a longstanding, butsomewhat ineffective, approach for reducing over-activity of the SNS.

As mentioned above, the renal sympathetic nervous system has beenidentified as a major contributor to the complex pathophysiology ofhypertension, states of volume overload (such as heart failure), andprogressive renal disease, both experimentally and in humans. Studiesemploying radiotracer dilution methodology to measure overflow ofnorepinephrine from the kidneys to plasma revealed increased renalnorepinephrine (NE) spillover rates in patients with essentialhypertension, particularly so in young hypertensive subjects, which inconcert with increased NE spillover from the heart, is consistent withthe hemodynamic profile typically seen in early hypertension andcharacterized by an increased heart rate, cardiac output, andrenovascular resistance. It is now known that essential hypertension iscommonly neurogenic, often accompanied by pronounced sympathetic nervoussystem overactivity.

Activation of cardiorenal sympathetic nerve activity is even morepronounced in heart failure, as demonstrated by an exaggerated increaseof NE overflow from the heart and the kidneys to plasma in this patientgroup. In line with this notion is the recent demonstration of a strongnegative predictive value of renal sympathetic activation on all-causemortality and heart transplantation in patients with congestive heartfailure, which is independent of overall sympathetic activity,glomerular filtration rate, and left ventricular ejection fraction.These findings support the notion that treatment regimens that aredesigned to reduce renal sympathetic stimulation have the potential toimprove survival in patients with heart failure.

Both chronic and end stage renal disease are characterized by heightenedsympathetic nervous activation. In patients with end stage renaldisease, plasma levels of norepinephrine above the median have beendemonstrated to be predictive for both all-cause death and death fromcardiovascular disease. This is also true for patients suffering fromdiabetic or contrast nephropathy. There is compelling evidencesuggesting that sensory afferent signals originating from the diseasedkidneys are major contributors to initiating and sustaining elevatedcentral sympathetic outflow in this patient group; this facilitates theoccurrence of the well known adverse consequences of chronic sympatheticover activity, such as hypertension, left ventricular hypertrophy,ventricular arrhythmias, sudden cardiac death, insulin resistance,diabetes, and metabolic syndrome.

(i) Renal Sympathetic Efferent Activity

Sympathetic nerves to the kidneys terminate in the blood vessels, thejuxtaglomerular apparatus and the renal tubules. Stimulation of therenal sympathetic nerves causes increased renin release, increasedsodium (Na+) reabsorption, and a reduction of renal blood flow. Thesecomponents of the neural regulation of renal function are considerablystimulated in disease states characterized by heightened sympathetictone and clearly contribute to the rise in blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome, which is renal dysfunction as a progressive complication ofchronic heart failure, with a clinical course that typically fluctuateswith the patient's clinical status and treatment. Pharmacologicstrategies to thwart the consequences of renal efferent sympatheticstimulation include centrally acting sympatholytic drugs, beta blockers(intended to reduce renin release), angiotensin converting enzymeinhibitors and receptor blockers (intended to block the action ofangiotensin II and aldosterone activation consequent to renin release)and diuretics (intended to counter the renal sympathetic mediated sodiumand water retention). However, the current pharmacologic strategies havesignificant limitations including limited efficacy, compliance issues,side effects and others.

(ii) Renal Sensory Afferent Nerve Activity

The kidneys communicate with integral structures in the central nervoussystem via renal sensory afferent nerves. Several forms of “renalinjury” may induce activation of sensory afferent signals. For example,renal ischemia, reduction in stroke volume or renal blood flow, or anabundance of adenosine enzyme may trigger activation of afferent neuralcommunication. As shown in FIGS. 3A and 3B, this afferent communicationmight be from the kidney to the brain or might be from one kidney to theother kidney (via the central nervous system). These afferent signalsare centrally integrated and may result in increased sympatheticoutflow. This sympathetic drive is directed towards the kidneys, therebyactivating the RAAS and inducing increased renin secretion, sodiumretention, volume retention and vasoconstriction. Central sympatheticover activity also impacts other organs and bodily structures innervatedby sympathetic nerves such as the heart and the peripheral vasculature,resulting in the described adverse effects of sympathetic activation,several aspects of which also contribute to the rise in blood pressure.

The physiology therefore suggests that (i) modulation of tissue withefferent sympathetic nerves will reduce inappropriate renin release,salt retention, and reduction of renal blood flow, and that (ii)modulation of tissue with afferent sensory nerves will reduce thesystemic contribution to hypertension and other disease statesassociated with increased central sympathetic tone through its directeffect on the posterior hypothalamus as well as the contralateralkidney. In addition to the central hypotensive effects of afferent renaldenervation, a desirable reduction of central sympathetic outflow tovarious other sympathetically innervated organs such as the heart andthe vasculature is anticipated.

B. Additional Clinical Benefits of Renal Denervation

As provided above, renal denervation is likely to be valuable in thetreatment of several clinical conditions characterized by increasedoverall and particularly renal sympathetic activity such ashypertension, metabolic syndrome, insulin resistance, diabetes, leftventricular hypertrophy, chronic end stage renal disease, inappropriatefluid retention in heart failure, cardio-renal syndrome, and suddendeath. Since the reduction of afferent neural signals contributes to thesystemic reduction of sympathetic tone/drive, renal denervation mightalso be useful in treating other conditions associated with systemicsympathetic hyperactivity. Accordingly, renal denervation may alsobenefit other organs and bodily structures innervated by sympatheticnerves, including those identified in FIG. 1. For example, as previouslydiscussed, a reduction in central sympathetic drive may reduce theinsulin resistance that afflicts people with metabolic syndrome and TypeII diabetics. Additionally, patients with osteoporosis are alsosympathetically activated and might also benefit from the downregulation of sympathetic drive that accompanies renal denervation.

C. Achieving Intravascular Access to the Renal Artery

In accordance with the present technology, neuromodulation of a leftand/or right renal plexus RP, which is intimately associated with a leftand/or right renal artery, may be achieved through intravascular access.As FIG. 4A shows, blood moved by contractions of the heart is conveyedfrom the left ventricle of the heart by the aorta. The aorta descendsthrough the thorax and branches into the left and right renal arteries.Below the renal arteries, the aorta bifurcates at the left and rightiliac arteries. The left and right iliac arteries descend, respectively,through the left and right legs and join the left and right femoralarteries.

As FIG. 4B shows, the blood collects in veins and returns to the heart,through the femoral veins into the iliac veins and into the inferiorvena cava. The inferior vena cava branches into the left and right renalveins. Above the renal veins, the inferior vena cava ascends to conveyblood into the right atrium of the heart. From the right atrium, theblood is pumped through the right ventricle into the lungs, where it isoxygenated. From the lungs, the oxygenated blood is conveyed into theleft atrium. From the left atrium, the oxygenated blood is conveyed bythe left ventricle back to the aorta.

As will be described in greater detail later, the femoral artery may beaccessed and cannulated at the base of the femoral triangle justinferior to the midpoint of the inguinal ligament. A catheter may beinserted percutaneously into the femoral artery through this accesssite, passed through the iliac artery and aorta, and placed into eitherthe left or right renal artery. This comprises an intravascular paththat offers minimally invasive access to a respective renal arteryand/or other renal blood vessels.

The wrist, upper arm, and shoulder region provide other locations forintroduction of catheters into the arterial system. For example,catheterization of either the radial, brachial, or axillary artery maybe utilized in select cases. Catheters introduced via these accesspoints may be passed through the subclavian artery on the left side (orvia the subclavian and brachiocephalic arteries on the right side),through the aortic arch, down the descending aorta and into the renalarteries using standard angiographic technique.

D. Properties and Characteristics of the Renal Vasculature

Since neuromodulation of a left and/or right renal plexus RP may beachieved in accordance with the present technology through intravascularaccess, properties and characteristics of the renal vasculature mayimpose constraints upon and/or inform the design of apparatus, systems,and methods for achieving such renal neuromodulation. Some of theseproperties and characteristics may vary across the patient populationand/or within a specific patient across time, as well as in response todisease states, such as hypertension, chronic kidney disease, vasculardisease, end-stage renal disease, insulin resistance, diabetes,metabolic syndrome, etc. These properties and characteristics, asexplained herein, may have bearing on the efficacy of the procedure andthe specific design of the intravascular device. Properties of interestmay include, for example, material/mechanical, spatial, fluiddynamic/hemodynamic and/or thermodynamic properties.

As discussed previously, a catheter may be advanced percutaneously intoeither the left or right renal artery via a minimally invasiveintravascular path. However, minimally invasive renal arterial accessmay be challenging, for example, because as compared to some otherarteries that are routinely accessed using catheters, the renal arteriesare often extremely tortuous, may be of relatively small diameter,and/or may be of relatively short length. Furthermore, renal arterialatherosclerosis is common in many patients, particularly those withcardiovascular disease. Renal arterial anatomy also may varysignificantly from patient to patient, which further complicatesminimally invasive access. Significant inter-patient variation may beseen, for example, in relative tortuosity, diameter, length, and/oratherosclerotic plaque burden, as well as in the take-off angle at whicha renal artery branches from the aorta. Apparatus, systems and methodsfor achieving renal neuromodulation via intravascular access shouldaccount for these and other aspects of renal arterial anatomy and itsvariation across the patient population when minimally invasivelyaccessing a renal artery.

In addition to complicating renal arterial access, specifics of therenal anatomy also complicate establishment of stable contact betweenneuromodulatory apparatus and a luminal surface or wall of a renalartery. When the neuromodulatory apparatus includes an energy deliveryelement, such as an electrode, consistent positioning and appropriatecontact force applied by the energy delivery element to the vessel wallare important for predictability. However, navigation is impeded by thetight space within a renal artery, as well as tortuosity of the artery.Furthermore, establishing consistent contact is complicated by patientmovement, respiration, and/or the cardiac cycle because these factorsmay cause significant movement of the renal artery relative to theaorta, and the cardiac cycle may transiently distend the renal artery(i.e., cause the wall of the artery to pulse.

Even after accessing a renal artery and facilitating stable contactbetween neuromodulatory apparatus and a luminal surface of the artery,nerves in and around the adventia of the artery should be safelymodulated via the neuromodulatory apparatus. Effectively applyingthermal treatment from within a renal artery is non-trivial given thepotential clinical complications associated with such treatment. Forexample, the intima and media of the renal artery are highly vulnerableto thermal injury. As discussed in greater detail below, theintima-media thickness separating the vessel lumen from its adventitiameans that target renal nerves may be multiple millimeters distant fromthe luminal surface of the artery. Sufficient energy should be deliveredto or heat removed from the target renal nerves to modulate the targetrenal nerves without excessively cooling or heating the vessel wall tothe extent that the wall is frozen, desiccated, or otherwise potentiallyaffected to an undesirable extent. A potential clinical complicationassociated with excessive heating is thrombus formation from coagulatingblood flowing through the artery. Given that this thrombus may cause akidney infarct, thereby causing irreversible damage to the kidney,thermal treatment from within the renal artery should be appliedcarefully. Accordingly, the complex fluid mechanics and thermodynamicconditions present in the renal artery during treatment, particularlythose that may impact heat transfer dynamics at the treatment site, maybe important in applying energy (e.g., heating thermal energy) and/orremoving heat from the tissue (e.g., cooling thermal conditions) fromwithin the renal artery.

The neuromodulatory apparatus should also be configured to allow foradjustable positioning and repositioning of the energy delivery elementwithin the renal artery since location of treatment may also impactclinical efficacy. For example, it may be tempting to apply a fullcircumferential treatment from within the renal artery given that therenal nerves may be spaced circumferentially around a renal artery. Insome situations, full-circle lesion likely resulting from a continuouscircumferential treatment may be potentially related to renal arterystenosis. Therefore, the formation of more complex lesions along alongitudinal dimension of the renal artery via the mesh structuresdescribed herein and/or repositioning of the neuromodulatory apparatusto multiple treatment locations may be desirable. It should be noted,however, that a benefit of creating a circumferential ablation mayoutweigh the potential of renal artery stenosis or the risk may bemitigated with certain embodiments or in certain patients and creating acircumferential ablation could be a goal. Additionally, variablepositioning and repositioning of the neuromodulatory apparatus may proveto be useful in circumstances where the renal artery is particularlytortuous or where there are proximal branch vessels off the renal arterymain vessel, making treatment in certain locations challenging.Manipulation of a device in a renal artery should also considermechanical injury imposed by the device on the renal artery. Motion of adevice in an artery, for example by inserting, manipulating, negotiatingbends and so forth, may contribute to dissection, perforation, denudingintima, or disrupting the interior elastic lamina.

Blood flow through a renal artery may be temporarily occluded for ashort time with minimal or no complications. However, occlusion for asignificant amount of time should be avoided because to prevent injuryto the kidney such as ischemia. It could be beneficial to avoidocclusion all together or, if occlusion is beneficial to the embodiment,to limit the duration of occlusion, for example to 2-5 minutes.

Based on the above described challenges of (1) renal arteryintervention, (2) consistent and stable placement of the treatmentelement against the vessel wall, (3) effective application of treatmentacross the vessel wall, (4) positioning and potentially repositioningthe treatment apparatus to allow for multiple treatment locations, and(5) avoiding or limiting duration of blood flow occlusion, variousindependent and dependent properties of the renal vasculature that maybe of interest include, for example, (a) vessel diameter, vessel length,intima-media thickness, coefficient of friction, and tortuosity; (b)distensibility, stiffness and modulus of elasticity of the vessel wall;(c) peak systolic, end-diastolic blood flow velocity, as well as themean systolic-diastolic peak blood flow velocity, and mean/maxvolumetric blood flow rate; (d) specific heat capacity of blood and/orof the vessel wall, thermal conductivity of blood and/or of the vesselwall, and/or thermal connectivity of blood flow past a vessel walltreatment site and/or radiative heat transfer; (e) renal artery motionrelative to the aorta induced by respiration, patient movement, and/orblood flow pulsatility: and (f) as well as the take-off angle of a renalartery relative to the aorta. These properties will be discussed ingreater detail with respect to the renal arteries. However, dependent onthe apparatus, systems and methods utilized to achieve renalneuromodulation, such properties of the renal arteries, also may guideand/or constrain design characteristics.

As noted above, an apparatus positioned within a renal artery shouldconform to the geometry of the artery. Renal artery vessel diameter,D_(RA), typically is in a range of about 2-10 mm, with most of thepatient population having a D_(RA) of about 4 mm to about 8 mm and anaverage of about 6 mm. Renal artery vessel length, L_(RA), between itsostium at the aorta/renal artery juncture and its distal branchings,generally is in a range of about 5-70 mm, and a significant portion ofthe patient population is in a range of about 20-50 mm. Since the targetrenal plexus is embedded within the adventitia of the renal artery, thecomposite Intima-Media Thickness, IMT, (i.e., the radial outwarddistance from the artery's luminal surface to the adventitia containingtarget neural structures) also is notable and generally is in a range ofabout 0.5-2.5 mm, with an average of about 1.5 mm. Although a certaindepth of treatment is important to reach the target neural fibers, thetreatment should not be too deep (e.g., >5 mm from inner wall of therenal artery) to avoid non-target tissue and anatomical structures suchas the renal vein.

An additional property of the renal artery that may be of interest isthe degree of renal motion relative to the aorta, induced by respirationand/or blood flow pulsatility. A patient's kidney, which located at thedistal end of the renal artery, may move as much as 4″ cranially withrespiratory excursion. This may impart significant motion to the renalartery connecting the aorta and the kidney, thereby requiring from theneuromodulatory apparatus a unique balance of stiffness and flexibilityto maintain contact between the thermal treatment element and the vesselwall during cycles of respiration. Furthermore, the take-off anglebetween the renal artery and the aorta may vary significantly betweenpatients, and also may vary dynamically within a patient, e.g., due tokidney motion. The take-off angle generally may be in a range of about30°-135°.

E. Achieving Renal Denervation Via an Intravascularly DeliveredMicrowave Field

Microwave energy may be utilized to achieve renal neuromodulation via atleast partial denervation of the kidney. For the purpose of thisdisclosure “microwave energy” and “microwave field” may be equivalentand interchangeable. Microwave energy is absorbed by tissue in a processcalled dielectric heating. Molecules in the tissue, such as watermolecules, are electric dipoles that have a positive charge at one endand a negative charge at the other. The microwave energy induces analternating electric field that causes the dipoles to rotate as theyattempt to align themselves with the field. This molecular rotationgenerates heat as the molecules hit one another and cause additionalmotion. The heating is particularly efficient with liquid watermolecules, which have a relatively high dipole moment. Tissue types thathave relatively low water content, such as fat, do not absorb microwaveenergy as efficiently as other types of tissue.

The friction and heat produced through dipole rotation increases tissuetemperature in a process known as dielectric heating, ultimately leadingto cell death (i.e., necrosis) via coagulation. Accordingly, one featureof microwave-induced dielectric heating is that such an arrangement isexpected to provide therapeutically high temperatures in target tissue,large and consistent ablation volumes, and/or relatively fast ablationtimes.

The renal arterial wall is comprised of intima, media and adventitia.Target renal nerves are positioned in and adjacent to the adventitia,and connective tissue surrounds the adventitia and nerves. Connectivetissue is largely comprised of fat, which is a poor absorber ofmicrowave energy due to its low water content, thereby reducing a riskof collateral damage to the fatty connective tissue during microwaveirradiation of the renal nerves.

A microwave transmission element positioned within the renal artery viaintravascular access may deliver a microwave field through the vesselwall and tissue, for example, omni-directionally in a plane relativelyperpendicular to the longitudinal axis of the vessel. The microwavefield may modulate (e.g., necrose), the target renal nerves. The depthto which the microwave field penetrates the wall and tissue is frequencydependent. Relatively greater microwave frequencies will providerelatively lower tissue penetration, while relatively lower microwavefrequencies will provide relatively greater tissue penetration.

When delivered intravascularly, preferentially heating the adventitiawhile avoiding significant thermal exposure to the intima/media may bechallenging. However, renal arterial blood flow may provide protectivecooling of the intima/media. Alternatively, open or closed circuitcooling may be utilized to remove excess heat from the inner wall of therenal artery. Various methods, systems and apparatuses for active andopen- and closed-circuit cooling have been described previously, forexample, in U.S. patent application Ser. No. 13/279,205, filed Oct. 21,2011, and International Patent App. No. PCT/US2011/033491, filed Apr.21, 2011, both of which are incorporated herein by reference in theirentireties.

II. Microwave Catheter Apparatuses, Systems, and Methods for RenalNeuromodulation A. Overview

As just described, the left and/or right RP surrounds the respectiveleft and/or right renal artery. The RP extends in intimate associationwith the respective renal artery into the substance of the kidney. FIG.5 shows a microwave system 10 for inducing neuromodulation viadielectric heating of the left and/or right RP by intravascular accessinto the respective left or right renal artery.

The microwave system 10 includes an intravascular treatment device 12such as a catheter with an elongated shaft 16 having a proximal endregion 18 and a distal end region 20. The proximal end region 18 of theelongated shaft 16 is connected to a handle assembly 200. The distal endregion 20 of the elongated shaft 16 carries at least one microwavetransmission element 24, such as a microwave antenna 100 (see FIG. 7).The elongated shaft 16 is sized and configured for placement of itsdistal end region 20 within a renal artery by intravascular access. Themicrowave transmission element 24 is also specially sized and configuredfor manipulation and use within a renal artery.

The microwave system 10 also includes a microwave source or generator26, such as a cavity magnetron, a klystron, a traveling wave tube, etc.Under the control of the caregiver or automated control algorithm 222,the microwave generator 26 generates a selected form and magnitude ofmicrowave energy. The generator preferably generates microwaves at amedically acceptable frequency, such as 915 MHz, 2.45 GHz, and/or 5.1GHz. As discussed previously, relatively greater microwave frequencieswill provide relatively lower tissue penetration, while relatively lowermicrowave frequencies will provide relatively greater tissuepenetration.

A feed or transmission line 28, such as a coaxial cable or a parallelwire, electrically transfers microwaves from the microwave generator 26to the microwave transmission element 24 (e.g., extends along or withinthe elongated shaft 16 from the generator 26 to the transmission element24). A control mechanism, such as foot pedal 110, can be connected(e.g., pneumatically or electrically) to the generator 26 to allow theoperator to initiate, terminate and, optionally, adjust variousoperational characteristics of the microwave generator 26, including,but not limited to, microwave energy delivery. Optionally, one or moresensors, such as one or more temperature (e.g., thermocouple,thermistor, etc.), impedance, pressure, optical, flow, chemical or othersensors, can be located proximate to or within the microwavetransmission element to monitor delivery of the microwave field and/orto monitor dielectric heating in the vicinity of the microwavetransmission element (see FIG. 22B).

As shown in FIG. 6A, the treatment device 12 provides access to the RPthrough an intravascular path 14 that leads to a respective renalartery. The handle assembly 200 is sized and configured to be securelyor ergonomically held and manipulated by a caregiver outside theintravascular path 14. By manipulating the handle assembly 200 fromoutside the intravascular path 14, the caregiver can advance theelongated shaft 16 through the sometimes tortuous intravascular path 14and remotely manipulate or actuate the distal end region 20 ifnecessary. Image guidance (e.g., CT, radiographic, IVUS, OCT, or anothersuitable guidance modality, or combinations thereof), can be used to aidthe caregiver's manipulation. Further, in some embodiments, imageguidance components (e.g., IVUS, OCT) may be incorporated into thetreatment device 12 itself.

As shown in FIG. 6B, the distal end region 20 of the elongated shaft 16can flex in a substantial fashion to gain entrance into a respectiveleft/right renal artery by manipulation of the elongated shaft 16.Optionally, the distal end region 20 of the elongated shaft 16 can gainentrance to the renal artery following a path defined by a guidecatheter, a guide wire, or a sheath (not shown). In such cases, themaximum outer dimension (e.g., diameter) of any section of the elongatedshaft 16, including the microwave transmission element 24 it carries,may be dictated by the inner diameter of the guide catheter throughwhich the elongated shaft 16 is passed. Assuming, for example, that an 8French guide catheter (which has an inner diameter of approximately0.091 inch (2.31 mm)) would likely be, from a clinical perspective, thelargest guide catheter used to access the renal artery, and allowing fora reasonable clearance tolerance between the elongated shaft 16 (i.e.,microwave transmission element 24, centering element 30, etc.) and theguide catheter, the maximum outer dimension can realistically beexpressed as being less than or equal to approximately 0.085 inch (2.16mm). However, use of a smaller 5 French guide catheter may require theuse of smaller outer diameters along the elongated shaft 16. Forexample, an elongated shaft 16 that is to be routed within a 5 Frenchguide catheter may have an outer dimension of no greater than 0.053 inch(1.35 mm). In another example, an elongated shaft 16 that is to berouted within a 6 French guide catheter may have an outer dimension ofno great than 0.070 inch (1.78 mm). In still further examples, othersuitable guide catheters may be used, and outer dimensions and/orarrangements of the treatment device 12 can vary accordingly.

Once entrance to a renal artery is gained, the microwave transmissionelement 24 optionally may be aligned with tissue along an interior wallof the respective renal artery. Optionally, the microwave transmissionelement 24 also may be centered within the renal artery via, forexample, an expandable centering element 30, such as a permeablecentering element, an expandable braid or mesh, a cage, a basket, aballoon, stabilizing members, prongs, etc., that may be remotelyexpanded and collapsed via the handle assembly 200. The centeringelement 30 has a low-profile delivery configuration for intravasculardelivery to, and retrieval from, within the renal artery (e.g., througha guide catheter), and an expanded deployed configuration (as seen inFIG. 6B) wherein the centering element 30 contacts the internal luminalsurface of the renal artery and centers the microwave transmissionelement 24 within the artery.

Once the microwave transmission element 24 is positioned as desiredwithin the renal artery, the purposeful application of microwave energyfrom the microwave generator 26 to tissue by radiation from themicrowave transmission element 24 induces one or more desiredneuromodulating effects on localized regions of the renal artery andadjacent regions of the RP, which lay intimately within or adjacent tothe adventitia of the renal artery. The purposeful application ofneuromodulating effects can achieve neuromodulation along all or aportion of the RP.

Neuromodulating effects can include thermal ablation, non-ablativethermal alteration, coagulation or damage (e.g., via sustained heatingand/or dielectric heating), and electromagnetic neuromodulation. Desireddielectric heating effects may include raising the temperature of targetneural fibers above a certain threshold to achieve non-ablative thermalalteration, or above a higher temperature to achieve ablative thermalalteration. For example, the target temperature can be above bodytemperature (e.g., approximately 37° C.) but less than about 45° C. fornon-ablative thermal alteration, or the target temperature can be about45° C. or higher for ablative thermal alteration. Desired non-thermalneuromodulation effects may include altering the electrical signalstransmitted in a nerve.

Specific embodiments of the microwave system 10, along with associatedmethods and apparatuses, will now be described in further detail. Theseembodiments are provided merely for the sake of illustration and shouldin no way be construed as limiting.

B. Specific Embodiments

1. Coaxial Cable Feed Line and Coaxial Antenna Microwave TransmissionElement

As discussed previously, microwaves are transferred from the microwavegenerator 26 to the microwave transmission element 24 via the feed line28. As seen, for example, in FIG. 7, the feed line 28 may comprise acoaxial cable 50, and the microwave transmission element 24 maycomprise, for example, a coaxial antenna 100. Coaxial cables andantennas are described, for example, in U.S. Pat. No. 2,184,729, toBailey, which is incorporated herein by reference in its entirety.Microwave catheters for use in cardiac ablation procedures andcomprising coaxial cables and antennas are described, for example, inU.S. Pat. No. 4,641,649 to Walinsky et al., which is incorporated hereinby reference in its entirety.

Antennas convert electric current into electromagnetic radiation (andvice versa). The coaxial antenna 100 is a type of dipole antenna. Thecoaxial cable 50 connects the microwave generator 26 to the coaxialantenna 100. The coaxial cable 50 comprises an inner conductor 52,insulation 54 coaxially disposed about the inner conductor, and an outerconductor 56 comprising a tubular metal braid or shield that iscoaxially disposed about the insulation 54. An outer delivery sheath orinsulation 58 may cover the outer conductor 56. Microwave energy isdelivered down the length of the coaxial cable 50 that terminates in theantenna 100 which is capable of radiating the energy into thesurrounding tissue. The microwave energy is delivered through the spacebetween the inner conductor 52 and the outer conductor 56. This spaceserves as a conduit while the outer conductor 56 prevents energy fromescaping. Where a gap is encountered in the outer conductor 56 microwaveenergy is applied to the surrounding tissues. The gap may be perceivedas an aperture instrumental in directing the microwave energy to thetarget in the controllable manner.

The insulation 54 between the inner and outer conductors 52, 56electrically insulates and maintains a uniform distance between theinner conductor 52 and the outer conductor 56. The insulation 54 maycomprise a dielectric material, such as solid or foamed PolyEthylene(PE) or PolyTetraFluoroEthylene (PTFE). The space between the inner andouter conductors 52, 56 may have an impedance that is approximatelymatched with the tissue impedance. An impedance mismatch between theantenna 100 and surrounding tissue may result in unbalanced currents onthe inner and outer conductors 52, 56 of the feed line 28. In this case,a remainder current may flow along the outside of the outer conductor 56of the feed line 28.

To form the coaxial antenna 100, an exposed element that is electricallyconnected to the inner conductor 52 is unshielded by the outer conductor56. For example, the exposed element may be an extension of the innerconductor 52 or an electrically conductive element that is electricallyconnected to the inner conductor 52. The length of the exposed elementmay be a fraction of the wavelength of the microwave radiation (i.e., afractional length), for example about ½ a wavelength. A distal region102 of the outer conductor 56 of the coaxial cable 50 optionally isexposed (i.e., outer insulation or sheath 58 is optional) over afractional length, for example, about ½ a wavelength. The distal regions102 and 104 form a radiating element 106 of dipole coaxial antenna 100.When driven by a microwave signal generated by generator 26 andtransferred by coaxial cable 50, the radiating element 106 of coaxialantenna 100 radiates microwaves outward in a torus or toroidal pattern.Microwave emission E is maximal and omni-directional in a planeperpendicular to the dipole (i.e., perpendicular to radiating element106) and substantially reduced in the direction of the dipole.

2. Expandable Multi-Filament Centering Elements

It may be desirable to heat the renal nerves disposed within theadventitia while avoiding significant dielectric heating of theintima/media during microwave irradiation. Renal arterial blood flow mayprovide passive protective cooling of the intima/media. Thus, thecentering element 30 may be permeable (such as in the expandablemesh/braid of FIG. 6B) and/or may not obstruct the entire vessel lumen,in order to ensure continued blood flow cooling of the renal arteryintima/media during microwave-induced dielectric heating of target renalnerves. The centering element 30, and/or some other element, also mayincrease the velocity of blood flow at or near the vessel wall toenhance or accelerate the transfer of heat from the wall to the blood.

In FIGS. 8A and 8B, an expandable centering element 830 comprises aplurality of resilient filaments 32 (e.g., fingers or prongs), which areconnected to the distal region 104 of inner conductor 52 at a connector34. The connector 34 may be conductive or non-conductive, such that thecentering element 830 may or may not, respectively, comprise a portionof the radiating element of an antenna 800. A nose cone 36 extends fromconnector 34, and all or a portion of the nose cone 36 also may or maynot be conductive (i.e., may or may not comprise a portion of theradiating element), as desired. In embodiments in which expandablecentering element 830 is not a portion of the radiating element, it maybe made from a dielectric material such as a polymer or ceramic.

As seen in FIG. 8A, in the low-profile delivery configuration, the outersheath 58 serves as a delivery sheath that extends and distally tapersto an attachment with the atraumatic nose cone 36, thereby constrainingfilaments 32. As seen in FIG. 8B, upon proximal retraction of thedelivery sheath (e.g., via actuation of the handle assembly 200), thefilaments 32 self-expand into contact with the vessel wall, therebycentering and aligning the coaxial antenna 800 with the longitudinalaxis of the vessel.

Microwave radiation from the microwave generator 26 then may betransferred along the coaxial cable 50 to the antenna 800 and radiatedomni-directionally into the vessel wall to target renal nerves. Themicrowaves dielectrically heat the target renal nerves, as discussedpreviously, which induces neuromodulation (e.g., denervation). Filaments32 of the centering element 830 do not significantly obstruct bloodflow, and thereby facilitate passive blood flow cooling of non-targetintima and media. Upon completion of renal neuromodulation, microwaveirradiation may be halted, and the centering element 830 may becollapsed for retrieval within the outer sheath 58 and/or within a guidecatheter.

With reference now to FIG. 9, an alternative embodiment of a centeringelement 930 is illustrated wherein filaments 32 are distally coupled tothe nose cone 36 to form an expandable basket 38. The basket 38 mayself-expand into contact with the vessel wall and/or may be activelyexpanded. FIG. 9 illustratively shows the basket 38 in the deployedconfiguration. Embodiments comprising expandable filaments or basketsfor centering elements 930 may have a multiple number of filaments 32(e.g., two, three, four, five, etc.), which may have variations ofgeometric shapes (e.g., straight, curved, helical, coiled, etc.).

3. Expandable Balloon Centering Elements

As seen in FIGS. 10A and 10B, an expandable centering element 1030optionally may comprise an expandable balloon 1040. The balloon 1040 maybe delivered in a low-profile configuration, expanded within the renalartery prior to and during application of the microwave field, and thencollapsed for retrieval. As illustrated in the side-sectional view ofFIG. 10A, expansion of the balloon 1040 into contact with the vesselwall may center an antenna 1000 within the vessel and align it with thelongitudinal axis of the vessel to facilitate omni-directional microwaveradiation into the wall. The balloon 1040 may be expanded by injecting afluid/gas (e.g. nitrogen, carbon dioxide, saline, or other suitableliquids or gases) through an injection lumen (see, e.g., injection lumen69 in FIG. 16). To contract the balloon the injected fluid or gas can beextracted through the same injection lumen, or through a separate lumen(not shown). A chilled fluid (e.g., chilled saline) may be used toinflate the balloon 1040 and may be circulated by injecting the fluidthrough an injection lumen and extracting the fluid through a separateextraction lumen to allow continuous or semi-continuous flow.Circulation of chilled fluid may have an added benefit of cooling thesurface layers of the artery while allowing the deeper adventitia andrenal nerves to heat and become neuromodulated (e.g., ablated).

As shown in FIG. 10A, a balloon may inflate to about the same diameteras the lumen of the artery and thereby occlude the artery (as shown inFIG. 10B). Alternatively (as illustrated in the cross-section of FIGS.11A and 11B), the balloon 1040 may not completely obstruct the lumen ofthe renal artery, thereby allowing blood flow to cool and protectnon-target intima and media during microwave irradiation of target renalnerves. By reducing the unobstructed cross-sectional area of thearterial lumen, the balloon 1040 may increase the velocity of blood flowthrough the unobstructed area, which may enhance the rate of heattransfer at the vessel wall along unobstructed portions of the lumen.

In FIG. 11A, a centering element 1130 a comprises a balloon 1140 ahaving two opposed lobes 42 that contact the inner wall of the renalartery. FIG. 11B illustrates an alternative embodiment of a centeringelement 1130 b comprising a balloon 1140 b having three lobes 42 spacedequidistantly about the circumference of the vessel. As will beapparent, balloons 1140 a, 1140 b may comprise any number of lobes, asdesired.

FIG. 12 illustrates another embodiment of an antenna 1200 having aplurality of balloons (illustrated individually as 1240 a and 1240 b)positioned proximal and distal of radiating section 106 of the antenna1200. Optionally, the balloons 1240 a and 1240 b comprise multiple lobesand do not fully obstruct the lumen of the renal artery. Providingproximal and distal balloons may better center the antenna 1200 withinthe renal artery.

In another embodiment as shown in FIG. 13, an expandable ballooncentering element 1340 and the distal region 104 of the inner conductor52 may be combined such that the distal region 104 comprises one or moreconductive electrode traces 55 applied on the surface of the balloon1340 for improved microwave energy delivery. In this example, theemitting antenna is the metallic spiral pattern 55 applied or depositedon the inner or outer surface of the balloon 1340. Balloons comprisingelectrodes have been fabricated, for example, by MicroPen Technologiesof Honeoye Falls, N.Y. The metallic spiral pattern 55 is electricallyconnected to the inner conductor 52 by a joint 57 that can be a weld ora solder joint. The antenna is thus implemented by a metalized pathprinted, deposited, or otherwise applied on the wall of the balloon 1340and can be joined to the inner conductor 52 of the coaxial cable by anextension of the inner conductor 52 or by a separate interconnectingwire (not shown).

As in previous examples to form the antenna, the distal region 104 ofthe inner conductor 52 of the coaxial cable 50 is exposed over a lengthequal to a fraction of the wavelength of the microwave radiation. Toachieve optimal length of the exposed inner conductor 52 and at the sametime achieve the desired dimensions of the distal region 104 of therenal artery catheter, it may be desired to have the exposed conductorlonger than the length of the balloon 1340. The proposed spiral patternachieved when the balloon is expanded and the antenna is unfurled, isone of the many metallic surface patterns that can be used to achievethe desired length of the antenna in a compact device suitable for renalartery deployment. Alternative zigzag patterns can be proposed, forexample, instead of a spiral. Common to these embodiments, the depositedmetal forms an antenna that is electrically connected to one of theconductors in the feed line and is longer than the length of theballoon. The shape of the field expected from these embodiments istoroidal and substantially similar to the microwave field produced bythe linear dipole antenna.

FIGS. 14 and 15 illustrate embodiments of antennas 1400 and 1500,respectively, where expandable balloon centering elements 1440 and 1540,respectively, comprise one or more conductive areas applied on thesurfaces of the balloons for improved microwave energy delivery, wherethe conductive areas are not electrodes but shields.

The inner conductor 52 is in electric connection with the exposedsegment of the antenna 1400, 1500 that is the emitter of the microwavefield and energy. The applied metallic patterns 1462, 1463, and 1564 arenot intended to emit energy but to reshape the microwave field and toimprove the antennae matching network and thus ultimately change thegeometry of the periarterial lesion. These designs can be useful whenthe toroidal shape of the microwave field is not desired in order topreferentially treat one area of the renal artery and spare another toreduce the risk of stenosis or for other medical reasons. In otherwords, to prevent direct penetration of microwaves into the tissuesurrounding the balloon catheter, the balloon envelope is provided witha metallic coating in selected areas. The metallic patterns 1462, 1463,and 1564 and other possible patterns (e.g., helical shielding patternsor shielding lines that are parallel to the axis of the vessel) distortthe microwave field and shield certain areas of the renal artery in apredictable fashion. The unprotected areas receive a relatively highconcentration of microwave energy.

FIG. 15 also illustrates incorporation of a conductive element 101 intoan atraumatic tip 1536. Such an element can be instrumental in tuning upthe antenna. The nose cone 1536 can incorporate a cap useful in the capand choke antennae designs intended to improve impedance matching. Thechoke is a conductive sleeve placed above the coaxial feed assemblyright before the area where the emitter antenna emerges from the coaxialshield.

FIG. 16 illustrates an embodiment of an antenna 1600 where a balloon1640 is asymmetric relative to the catheter shaft and the antenna 1600.The purpose of such a balloon 1640 is to increase the delivery ofmicrowave energy to one side of the internal lumen of the renal arteryand decrease the delivery to the opposite side.

4. Flow Directing Elements

FIG. 17 illustrates an embodiment of a microwave system 1710 comprisingan expandable centering element 1730 in combination with a flowdirecting velocity enhancement element 1745. In FIG. 17, the centeringelement 1730 illustratively comprises multiple resilient filaments 32,as discussed previously. Flow directing element 1745 illustrativelycomprises an expandable balloon having a diameter less than the diameterof the lumen of the renal artery in which treatment is conducted.Microwave transmitting element 24/antenna 1700 may be positioned withinthe flow directing element 1745.

In the expanded deployed configuration of FIG. 17, the centering element1730 aligns and centers the antenna 1700 within the renal artery, whilethe flow directing element 1745 obstructs the center of the artery. Thiscentral obstruction directs blood flow around the flow directing element1745 and toward the luminal wall of the renal artery, where protectivecooling is desired during microwave irradiation and dielectric heatingof the target renal nerves. The central obstruction also increases flowvelocity, which in turn increases the rate of protective heat transferfrom the vessel wall to the blood during such microwave irradiation.

5. Over-the-Wire and Rapid Exchange Microwave Catheters

It may be desirable for the microwave system 10 to comprise anintravascular treatment device 12 configured for delivery over a guidewire. In any of the previously described embodiments, the coaxial cable50 and coaxial antenna 100 may be modified such that the inner conductor52 comprises a tubular inner conductor with a guide wire lumen (e.g., acoiled tube, a braided metal tube, or a flexible polymer tube coatedwith a conductive material, such as silver). For example, FIG. 18Aillustrates an alternative embodiment of the microwave system of FIG. 7having an antenna 1800 wherein the inner conductor 52 comprises atubular inner conductor having a guide wire lumen 53. In the embodimentillustrated in FIG. 18A, the guide wire lumen 53 extends completelythrough the shaft 16 from the proximal opening of the shaft 16 at anadaptor (e.g., at the handle 200 shown in FIG. 5) to the distal openingof the shaft 16 in an over-the-wire (OTW) configuration, whereas in theembodiment illustrated in FIG. 18B, a guide wire 183 and the guide wirelumen 53 extend through only a portion of the shaft 16 in a rapidexchange (RX) configuration. Although the proximal end of the guide wirelumen 53 is shown in FIG. 18B extending through the sidewall of theshaft 16 at the distal region 20, in other embodiments, the proximal endof the guide wire lumen 53 can be accessible anywhere between theproximal and distal ends of the shaft 16. The guide wire lumen 53 shownin FIGS. 18A and 18B, or variations thereof, may be included in variousembodiments described herein to facilitate navigation through thevasculature. Suitable OTW and RX guide wire configurations are disclosedin U.S. Pat. No. 5,545,134, filed Oct. 27, 1994, U.S. Pat. No.5,782,760, filed May 23, 1995, U.S. Patent App. Publication No. US2003/0040769, filed Aug. 23, 2001, and U.S. Patent App. Publication No.US 2008/0171979, filed Oct. 17, 2006, each of which is incorporatedherein by reference in its entirety.

6. Inner Conductors with Dynamically Variable Exposed Length

When utilizing a coaxial antenna, it may be desirable to provide theinner conductor 52 with a dynamically variable exposed length in orderto better match the antenna to the surrounding media (i.e., blood andtissue). Media matching depends on multiple factors, includingelectrical characteristics of the media (e.g., dielectric properties),frequency of the microwave signal, and power of the microwave signal, aswell as geometrical parameters of the radiating element 106 of theantenna. Dynamically varying the exposed length of the inner conductor52 dynamically varies the geometrical parameters of the radiatingelement 106, which may be utilized to facilitate better media matching.

Referring now to FIGS. 19A and 19B, in one embodiment, a coaxial antenna1900 may comprise an adjustable gap for dynamically varying the exposedlength of the inner conductor 52. As seen in FIG. 19A, the distal regionof outer conductor 56 may comprise a first outer conductor 56 a and asecond outer conductor 56 b spaced longitudinally from the first outerconductor 56 a. Likewise the (dielectric) insulation 54 comprises afirst insulation 54 a and a second insulation 54 b spaced longitudinallyfrom the first insulation 54 a. The outer sheath 58 is attached to thesecond outer conductor 56 b, but may freely slide relative to firstouter conductor 56 a.

In FIG. 19A, radiating element 106 of antenna 1900 comprises the exposedportion of inner conductor 52 positioned between the first and secondouter conductors. As seen in FIG. 19B, proximal retraction of outersheath 58 proximally retracts the second outer conductor 56 b and thesecond insulation 54 b relative to the inner conductor 52, therebydynamically altering the radiating element 106 of the antenna 1900. Aswill be apparent, in an alternative embodiment, the microwave system ofFIGS. 19A and 19B may be modified such that the inner conductor 52comprises a tubular inner conductor having a guide wire lumen tofacilitate over-the-wire delivery of the treatment device 12. Themicrowave system may alternatively be modified for RX delivery of thetreatment device 12.

FIG. 20 illustrates another embodiment of an antenna 2000 having aninner conductor 52 with a dynamically variable exposed length distalregion 104. In FIG. 20, the exposed length along the distal region 104of the inner conductor 52 includes a conductive wire loop 60 that loopsback and extends within a lumen 61 through an elongated shaft 16 of anintravascular treatment device 12. As illustrated by dotted lines inFIG. 20, the medical practitioner may dynamically extend and retract thewire loop 60 to dynamically vary the exposed length of the innerconductor 52.

FIGS. 21A and 21B illustrate an over-the-wire embodiment of a microwavesystem having an inner conductor 52 with a dynamically variable exposedlength. As seen in FIG. 21A, the distal end region 20 of the elongatedshaft 16 having a coaxial antenna 2100 with tubular inner conductor 52having a guide wire lumen 53 may be advanced over a guide wire 108 intothe renal artery. As seen in FIG. 21B, the guide wire 108 then may beremoved and replaced with a radiator 70 that is electrically coupled tothe tubular inner conductor 52. The radiator 70 may, for example,comprise protrusions that contact the inner wall of the inner conductor52 to electrically couple to the tubular inner conductor 52.

The radiator 70 extends beyond the distal end region 20 of the elongatedshaft 16 to form the exposed distal region 104 of the inner conductor52, thereby forming a portion of the radiating element 106 of theantenna 2100 during microwave irradiation of the renal nerves. Thelength of the exposed distal region 104 of inner conductor 52 may bevaried by dynamically varying how far the radiator 70 extends beyonddistal end region 20 of elongated shaft 16.

7. Active Cooling

In addition to the passive cooling provided by blood flow, activecooling may be provided in the vicinity of the microwave transmissionelement via a coolant (e.g., a circulating coolant). For example, asseen in FIG. 22A, a coolant 112 may be introduced into an annular spacebetween the coaxial cable 50 and dielectric or insulator 2258. As seenin FIG. 22B, the annular space may extend over a coaxial antenna 2200.Optionally, the coolant may be circulated to enhance heat transfer.Optionally, a temperature sensor, such as a thermistor or thermocouple59, may be positioned within the coolant in the vicinity of theradiating element of the antenna 2200 to monitor temperature.Temperature data collected with the temperature sensor may be utilizedin a feedback loop to control or alter delivery of the microwave fieldand/or the coolant in response to the measured temperature (e.g., tomaintain the temperature within a desired range).

Additionally or alternatively, the inner layers of an artery may bespared from heat if microwave energy is delivered in pulses. Duringpauses of energy delivery, blood will flow away from the area of energyapplication and be replaced by colder blood. At the same time tissuessurrounding the inner lumen of the artery will continue to accumulateheat leading to the desired targeted tissue destruction. Pulsed deliveryof microwave energy can be achieved by setting the duty cycle of themicrowave energy generator. The thermal inertia of the targeted tissueswill ensure the desired build up of heat while sparing the inner lumenof the blood vessel.

8. Directed Application of a Microwave Field

The specific embodiments described above provide toroidal-shaped,omni-directional emission of microwaves from a microwave transmissionelement 24 (i.e., from the radiating element 106 of coaxial antenna100). While such an omni-directional microwave energy depositiondelivered intravascularly may desirably provide a circumferentialtreatment about the renal artery, it may be desirable under certaincircumstances to target a specific non-circumferential area (e.g., tomore narrowly direct application of the microwave energy deposition tospecific target renal nerves). Thus, a microwave transmission element 24may include shielding or other means for directional application ofmicrowave energy.

For example, FIG. 23A illustrates a shielding 65 substantiallysurrounding the radiating element 106 of the coaxial antenna 100. FIGS.23B and 23C are cross-sectional views of the antenna 100 along lines B-Band C-C, respectively. Referring to FIGS. 23A-23C, the shielding 65includes a window 21 through which the microwave emissions E may bedirected. The window 21 can take up various proportions of thecircumference of the shielding 65. For example, in one embodiment, thewindow 21 comprises approximately 30% of the circumference of theshielding 65 over the length of the emitting portion of the antenna 100.In further embodiments, the window 21 can comprise more or less of thecircumference of the shielding 65 and can extend only part of the lengthof the emitting portion of the antenna 100. In some embodiments, it maybe desirable for the shielding 65 to possess reflective properties suchthat a substantial portion of the omni-directional field that encountersthe shielding 65 is redirected through the window 21. In furtherembodiments, the shielding 65 can include more than one window (e.g.,multiple longitudinally offset windows facing opposite directions, or ahelical window, etc.). The lesion geometry will accordingly match thewindow geometry.

In some embodiments, it may also be desirable for the elongated shaft 16(FIG. 5) to have deflection capability at or near its distal region 20proximal of the antenna 100 to facilitate positioning of the shieldingwindow 21 within the renal artery. For example, as illustrated in FIGS.23D and 23E, deflection capability may be provided by a control wire 23running through the catheter from the handle to or near the distalregion 20 proximal of the antenna 100, where the catheter includes aflexibly biased structure such as a laser cut tube 25. When the controlwire 23 is pulled or pushed by an actuator in the handle (not shown),the flexibly biased structure is deflected in the flexibly biaseddirection.

In one embodiment, pulling or pushing the control wire 23 can cause thedistal region 20 to deflect in the direction of the window 21 tofacilitate positioning of the window 21 in substantial contact with thevessel wall (as illustrated in FIG. 23E). In another embodiment, pullingor pushing the control wire 23 can cause the catheter to deflect in adirection opposite that of the window 21 to ensure that there issufficient space between the window 21 and targeted area of the vesselwall to allow for blood flow to cool non-target intima/media tissue.Other embodiments disclosed herein (e.g., balloon-centeringembodiments), can similarly employ an elongated shaft 16 havingdeflection capabilities to control positioning of the antenna 100 in therenal artery.

III. Conclusion

Although the specific embodiments of a microwave system have beendescribed with a feed line comprising a coaxial cable and a microwavetransmission element comprising a coaxial antenna, it should beunderstood that any alternative feed lines and microwave transmissionelements may be utilized. For example, a feed line may comprise aparallel wire. Likewise, a microwave transmission element may, forexample, comprise a waveguide or an alternative type of antenna, such asa patch antenna, a slot antenna, another form of dipole antenna, aYagi-Uda antenna, a parabolic antenna, etc.

The above detailed descriptions of embodiments of the technology are notintended to be exhaustive or to limit the technology to the precise formdisclosed above. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. The variousembodiments described herein may also be combined to provide furtherembodiments.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Where thecontext permits, singular or plural terms may also include the plural orsingular term, respectively. Additionally, the term “comprising” is usedthroughout to mean including at least the recited feature(s) such thatany greater number of the same feature and/or additional types of otherfeatures are not precluded. It will also be appreciated that specificembodiments have been described herein for purposes of illustration, butthat various modifications may be made without deviating from thetechnology. Further, while advantages associated with certainembodiments of the technology have been described in the context ofthose embodiments, other embodiments may also exhibit such advantages,and not all embodiments need necessarily exhibit such advantages to fallwithin the scope of the technology. Accordingly, the disclosure andassociated technology can encompass other embodiments not expresslyshown or described herein.

1-20. (canceled) 21: A catheter apparatus comprising: an elongated bodyextending from a proximal end to a distal end, wherein the elongatedbody is configured to be intravascularly positioned within a renalartery of a patient; an expandable centering element coupled to a distalportion of the elongated body; and a transmitting element carried by theexpandable centering element, wherein the expandable centering elementis configured to expand to center the transmitting element within therenal artery without fully occluding blood flow through the renalartery, wherein the transmitting element is configured toomni-directionally radiate energy in a plane perpendicular to thetransmitting element to thermally affect a renal nerve along the renalartery of the patient, and wherein expanding centering element isconfigured to receive a fluid to actively cool the transmitting elementwhile the transmitting element is omni-directionally radiating energy.22: The catheter apparatus of claim 21, wherein the transmitting elementis a microwave antenna. 23: The catheter of claim 22, wherein themicrowave antenna comprises a coaxial antenna. 24: The catheter of claim23, wherein the coaxial antenna includes a radiating element comprisinga dynamically varying length. 25: The catheter of claim 24, furthercomprising a shielding element configured to shield a portion of theradiating element to preferentially direct the omni-directionallyradiated energy. 26: The catheter of claim 21, wherein the expandablecentering element is further configured to redirect blood flowingthrough the renal artery while in an expanded configuration. 27: Thecatheter of claim 26, wherein the expandable centering element isfurther configured to increase a velocity of the blood flow near a wallof the renal artery to enhance a rate of heat transfer between the walland the blood flow. 28: The catheter of claim 21, further comprising atleast one temperature sensor configured to sense a temperature of thetransmitting element. 29: The catheter of claim 21, further comprisingat least one temperature sensor configured to sense a temperature oftissue adjacent the renal artery. 30: The catheter of claim 21, whereinthe transmitting element is configured to dielectrically heat the renalnerve to induce necrosis in the renal nerve. 31: A system comprising: acatheter apparatus comprising: an elongated body extending from aproximal end to a distal end, wherein the elongated body is configuredto be intravascularly positioned within a renal artery of a patient; anexpandable centering element coupled to a distal portion of theelongated body; and a transmitting element carried by the expandablecentering element, wherein the expandable centering element isconfigured to expand to center the transmitting element within the renalartery without fully occluding blood flow through the renal artery,wherein the transmitting element is configured to omni-directionallyradiate energy in a plane perpendicular to the transmitting element tothermally affect a renal nerve along the renal artery of the patient,and wherein expanding centering element is configured to receive a fluidto actively cool the transmitting element while the transmitting elementis omni-directionally radiating energy; and a generator external to thepatient, wherein the generator is coupled to the transmitting elementand is configured to generate and deliver energy to the transmittingelement. 32: The system of claim 31, wherein the transmitting element isa microwave transmitting element comprising a coaxial antenna, whereinthe generator is a microwave generator, wherein the system furthercomprises a coaxial cable coupling the microwave generator to thecoaxial antenna. 33: The system of claim 32, wherein the coaxial antennaincludes a radiating element comprising a dynamically varying length.34: The system of claim 33, wherein the catheter apparatus furthercomprises a shielding element configured to shield a portion of theradiating element to preferentially direct the omni-directionallyradiated energy. 35: The system of claim 31, wherein the expandablecentering element is further configured to redirect blood flowingthrough the renal artery while in an expanded configuration. 36: Thesystem of claim 35, wherein the expandable centering element is furtherconfigured to increase a velocity of the blood flow near a wall of therenal artery to enhance a rate of heat transfer between the wall and theblood flow. 37: The system of claim 31, further comprising a guide wireover which the catheter apparatus is configured to be advanced. 38: Thesystem of claim 31, wherein the catheter apparatus further comprises atleast one temperature sensor configured to sense a temperature of thetransmitting element. 39: The system of claim 31, wherein the catheterfurther comprises at least one temperature sensor configured to sense atemperature of tissue adjacent the renal artery. 40: The system of claim31, wherein the transmitting element is configured to dielectricallyheat the renal nerve to induce necrosis in the renal nerve.